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Updated: May 22, 2025
Ovarian Cancer Patient-Derived Organoid Models for Pre-Clinical Drug Testing
Published on: September 15, 2023
A patient-derived ovarian cancer organoid platform to study susceptibility to natural killer cells
Marisa Mercadante1, Armin Scheben1, Jacob Estrada1
1The New York Stem Cell Foundation Research Institute, New York, NY.
Abstract:
Intratumoral heterogeneity drives therapy resistance and relapses in advanced stage cancers, such as ovarian cancer. Here, we present a live cell imaging assay using patient-derived ovarian cancer organoids for real time capture and quantification of natural killer cell-mediated apoptotic events in >500 organoids simultaneously. Our assay revealed significant inter- and intratumor response heterogeneity and identified a rare resistant organoid population, opening avenues to test immunomodulatory strategies that overcome resistance.
Insights
Intratumoral heterogeneity in ovarian cancer organoids causes therapy resistance. A new live imaging assay quantifies natural killer cell responses, revealing rare resistant cells and guiding new immunotherapies.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Intratumoral heterogeneity is a key driver of therapy resistance and relapse in advanced cancers, including ovarian cancer.
- Understanding cellular responses to therapy is crucial for developing effective treatment strategies.
Purpose of the Study:
- To develop and validate a live cell imaging assay for real-time quantification of natural killer (NK) cell-mediated apoptosis in patient-derived ovarian cancer organoids.
- To investigate inter- and intratumor heterogeneity in NK cell responses within ovarian cancer organoids.
Main Methods:
- Utilization of patient-derived ovarian cancer organoids.
- Development of a high-throughput live cell imaging assay capable of simultaneously monitoring over 500 organoids.
- Real-time capture and quantification of natural killer cell-mediated apoptotic events.
Main Results:
- The assay successfully captured and quantified NK cell-mediated apoptotic events in a large number of organoids.
- Significant inter- and intratumor heterogeneity in response to NK cell activity was observed.
- Identification of a rare subpopulation of organoids exhibiting resistance to NK cell-mediated apoptosis.
Conclusions:
- The developed live cell imaging assay is a powerful tool for dissecting heterogeneity in cancer immunotherapy response.
- The findings highlight the presence of resistant ovarian cancer cell populations, underscoring the need for strategies to overcome resistance.
- This assay provides a platform for testing novel immunomodulatory strategies aimed at enhancing NK cell efficacy against resistant tumors.
